APE1/Ref-1 siRNA inhibits IL-6 and IL-8 secretion by cultured bone marrow stromal cells isolated from multiple myeloma patients

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APE1/Ref-1 siRNA inhibits IL-6 and IL-8 secretion by cultured bone marrow stromal cells isolated from multiple myeloma patients

更新时间：2026-01-09

- APE1/Ref-1 siRNA inhibits IL-6 and IL-8 secretion by cultured bone marrow stromal cells isolated from multiple myeloma patients
- Journal of Army Medical University Vol. 31, Issue 19, Pages: 1850-1853(2009)
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  CLC： R392.11;R394.3;R733.3
- Published：2009
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谢家印,王东,李梦侠,向德兵,杨镇洲,杨宇馨,李增鹏,曾林立,仲召阳,王阁.APE1/Ref-1 siRNA抑制多发性骨髓瘤骨髓基质细胞IL-6及IL-8分泌的体外研究[J].陆军军医大学学报(原第三军医大学学报),2009,31(19):1850-1853.

　XIE Jia-yin,WANG Dong,LI Meng-xia,XIANG De-bing,YANG Zhen-zhou,YANG Yu-xin,LI Zeng-peng,ZENG Lin-li,ZHONG Zhao-yang,WANG Ge.APE1/Ref-1 siRNA inhibits IL-6 and IL-8 secretion by cultured bone marrow stromal cells isolated from multiple myeloma patients[J].J Amry Med Univ (J Third Mil Med Univ),2009,31(19):1850-1853.
谢家印,王东,李梦侠,向德兵,杨镇洲,杨宇馨,李增鹏,曾林立,仲召阳,王阁.APE1/Ref-1 siRNA抑制多发性骨髓瘤骨髓基质细胞IL-6及IL-8分泌的体外研究[J].陆军军医大学学报(原第三军医大学学报),2009,31(19):1850-1853. DOI：

　XIE Jia-yin,WANG Dong,LI Meng-xia,XIANG De-bing,YANG Zhen-zhou,YANG Yu-xin,LI Zeng-peng,ZENG Lin-li,ZHONG Zhao-yang,WANG Ge.APE1/Ref-1 siRNA inhibits IL-6 and IL-8 secretion by cultured bone marrow stromal cells isolated from multiple myeloma patients[J].J Amry Med Univ (J Third Mil Med Univ),2009,31(19):1850-1853. DOI：

摘要

目的体外通过APE1/Ref-1 siRNA敲低多发性骨髓瘤骨髓基质细胞(bone marrow stromal cells

BMSCs) APE1/Ref-1的表达，观察BMSCs的增殖及分泌细胞因子IL-6、IL-8的变化，初步探讨BMSCs APE1/Ref-1表达的功能特点。方法通过免疫细胞化学染色法定量检测35例初治、11例复发/难治多发性骨髓瘤患者及10例正常人BMSCs APE1/Ref-1的表达特点及其差异，经Adv5-APE1/Ref-1 siRNA感染BMSCs后，流式细胞仪检测BMSCs细胞周期的变化；ELISA法检测BMSCs分泌IL-6、IL-8的水平变化情况。结果多发性骨髓瘤BMSCs的APE1/Ref-1蛋白阳性表达率显著高于正常BMSCs APE1/Ref-1蛋白阳性表达率（P0.05)，且多发性骨髓瘤BMSCs的APE1/Ref-1呈细胞核及核浆共同表达方式。Adv5-APE1/Ref-1 siRNA感染敲低多发性骨髓瘤及正常BMSCs APE1/Ref-1的表达量呈进行性减少 (P0.01)，同时发现APE1/Ref-1 siRNA对多发性骨髓瘤BMSCs抑制作用更明显。Adv5-APE1/Ref-1 siRNA感染BMSCs 后对正常人及骨髓瘤患者BMSCs分泌细胞因子IL-6、IL-8的量有显著的抑制作用，特别是感染72 h后，骨髓瘤患者及正常人的BMSCs 分泌IL-6[初治患者（246.29±46.51）pg/ml，复发/难治患者（365.09±75.25）pg/ml]、IL-8[初治患者（118.77±18.08） pg/ml，复发/难治患者（188.71±33.76）pg/ml]的量最低，与其他时段比较差异有统计学意义（P0.01）。结论多发性骨髓瘤BMSCs APE1/Ref-1的表达特点不同于正常BMSCs，可能导致其功能差异；APE1/Ref-1 siRNA敲低了MM BMSCs APE1/Ref-1的表达，同时明显抑制了其IL-6、IL-8的分泌，减少了对骨髓瘤细胞的促增殖和凋亡作用。

Abstract

Objective To explore the possible roles of apurinic/apyrimidinic endonuclease 1/redox factor-1 (APE1/Ref-1) expression in the bone marrow stromal cells (BMSCs) form multiple myeloma (MM) patients. Methods The expression of APE1/Ref-1 protein in BMSCs isolated from the bone marrow samples of 35 initial cases

11 relapse/refractory cases with MM and 10 cases health individuals were detected by immunocytochemistry. Before and after the transfection of the adenoviral vector Adv5-APE1/Ref-1 siRNA

the concentrations of interleukin-6 (IL-6) and interleukin-8 (IL-8) in the supernatant of BMSCs were measured with ELISA

and the cell cycles proliferation of BMSCs were detected with flow cytometry. Results The expression of APE1/Ref-1 protein in the cultured BMSCs was significantly higher than in normal BMSCs (P0.05). APE1/Ref-1 siRNA obviously inhibited the expression of the protein in MM or normal BMSCs. Transfected with Adv5-APE1/Ref-1 siRNA

the MM or normal BMSCs gradually decreased the levels of IL-6 and IL-8 secretion in a time course. In 72 h after the transfection

the amounts of IL-6 and IL-8 in the BMSCs supernatant reached the lowest levels as following

IL-6 (246.29±46.51) pg/ml and IL-8 (118.77±18.08) pg/ml in initial MM group

and IL-6 (365.09±75.25) pg/ml and IL-8 (188.71±33.76) pg/ml in relapse/refractory group (P0.01). Conclusion The abnormal expression of APE1/Ref-1 protein in MM BMSCs may lead to many changes of biological function. APE1/Ref-1 siRNA knocks down the expression of APE1/Ref-1 protein in BMSCs

and inhibits the production of IL-6 and IL-8 in MM BMSCs

thus indirectly reduces the proliferation or benefit apoptosis of myeloma cells.

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